The x-ray crystallographic structure determination of the large polypeptide hormone, human chorionic somatomammotropin (HCS) will be continued. HCS belongs to the protein family which also includes the two pituitary hormones, growth hormone and prolactin, and itself possesses both growth-promoting and lactogenic activities. An initial electron density map at 3.5 A resolution, based on phases derived from isomorphous replacement, anomalous scattering and solvent levelling techniques, is being interpreted using the graphics program FRODO. The quality of this map will be improved and the resolution extended to the limit of diffraction, better than 3.0 A, followed by Hendrickson-Konnert least squares refinement. Such a structure will yield a trial model for the related growth hormones and prolactins. One of these, human growth hormone, is of considerable clinical importance, and another, bovine growth hormone, is becoming of agronomic importance. A new purification scheme has been developed for bovine growth hormone, which has enabled very small, but well-ordered single crystals to be grown, the first for any pituitary hormone. Data will be collected on such crystals at the Cornell high-energy synchrotron x-ray source, CHESS, using oscillation techniques, initially to 3.2 A resolution. The structure determination of bovine growth hormone will be pursued by conventional as well as unconventional x-ray crystallographic techniques, with the goal of a refined structure at less than 3.0 A resolution. Similar purification schemes will be developed for prolactins from bovine, ovine and porcine species, and for growth hormones from the last two; crystallization will be attempted. Using protein either purified ourselves or supplied by others, crystals will also be sought of the S100 calcium-binding proteins from bovine brain; of calcineurin; of chicken intestinal calcium binding protein; of human growth hormone; and of bovine or porcine intestinal calcium binding proteins depleted in calcium. If crystallizations prove successful, structure determination will be initiated. Calculations will be performed of the electrostatic potential and the electric field around calcium binding proteins of known structure, to investigate possible electrostatic effects in cation binding, and in intermolecular interactions.